DESCRIPTION (Verbatim from the Applicant's Abstract): Surgical intervention, by its very nature, results in tissue damage that triggers the formation of fibrotic scar tissue as part of the normal wound healing response. Although inflammation and production of extracellular matrix components is necessary for normal wound healing, adhesions may also occur which can lead to significant clinical complications. For instance, after laminectomy, fibrotic scarring can develop in both the epidural region and arachnoid spaces, producing recurring pain and restriction of mobility. Simple bioresorbable barriers made from hyaluronic acid, regenerated cellulose, or collagen films or gels have been shown to have some efficacy in preventing inter-tissue adhesions, but there are still a significant number of adhesions that occur using this strategy. Another strategy to eliminate post-surgical adhesions is to provide an agent, which inhibits collagen production, the main protein component of scar tissue. For example, cis -4 - hydroxyproline (cHyp) has been shown to be a potent inhibitor of synthesis of collagen, and thus has been considered as a potential antifibrotic agent. In previous studies, cHyp was attached to a water-soluble polymer (denoted as poly [PEG-Lys-cHyp]) to provide a sustained release formulation. The lysine component has a free carboxylic acid pendent group at each monomeric repeat unit that can be used to couple active agents such as cHyp. The polymers were found to sustain release, reduce toxicity, and increase antifibrotic potency of attached cHyp in preliminary studies. A series of in vitro and in vivo studies has established the use of this polymer for the delivery of cHyp, showing that collagen production can be effectively inhibited without other cytotoxic effects. The scientific objectives of this Phase I proposal is to establish a formulation of the poly [PEG-Lys-cHyp] polymer that can be used to prevent post-surgical adhesion formation. A well-described animal model emulating neurosurgery will be utilized to develop an effective formulation. PROPOSED COMMERCIAL APPLICATION: A number of approaches have been pursued to limit the complication of post-surgical adhesions, such as the use of nonresorbable and resorbable barriers, and using active agents to inhibit or minimize adhesion formation. Despite the product development activity in this field, there are currently only a few products available for clinical use, with neither product reducing adhesions by more than 55%. An effective product would have a major impact on patient morbidity and health care economics.